Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents

This Article Full Text Full Text (PDF, 111K) PPT slides of all figures Alert me when this article is cited Citation Map Services Email this article Similar articles in this journal Similar articles in PubMed Alert me to new content in the JEM Download to citation manager Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Broxmeyer, H. E. Articles by Murphy, P. M. Search for Related Content PubMed PubMed Citation Articles by Broxmeyer, H. E. Articles by Murphy, P. M. Social Bookmarking                            What's this?

Brief Definitive Reports

Hal E. Broxmeyer^*,, Scott Cooper^*,, Giao Hangoc^*,, Ji-Liang Gao, and Philip M. Murphy

From the ^* Department of Microbiology/Immunology, the Department of Medicine, and the Walther Oncology Center, Indiana University School of Medicine, Indianapolis, Indiana 46202; the Walther Cancer Institute, Indianapolis, Indiana 46208; and the Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892

Macrophage inflammatory protein (MIP)-1, a CC chemokine, enhances proliferation of mature subsets of myeloid progenitor cells (MPCs), suppresses proliferation of immature MPCs, and mobilizes mature and immature MPCs to the blood. MIP-1 binds at least three chemokine receptors. To determine if CCR1 was dominantly mediating the above activities of MIP-1, CCR1-deficient (–/–) mice, produced by targeted gene disruption, were used. MIP-1 enhanced colony formation of marrow granulocyte/macrophage colony-forming units (CFU-GM), responsive to stimulation by granulocyte/macrophage colony-stimulating factor (GM-CSF), and CFU-M, responsive to stimulation by M-CSF, from littermate control CCR1^+/+ but not CCR1^–/– mice. Moreover, MIP-1 did not mobilize MPCs to the blood or synergize with G-CSF in this effect in CCR1^–/– mice. However, CCR1^–/– mice were increased in sensitivity to MPC mobilizing effects of G-CSF. Multi-growth factor–stimulated MPCs in CCR1^–/– and CCR1^+/+ marrow were equally sensitive to inhibition by MIP-1. These results implicate CCR1 as a dominant receptor for MIP-1 enhancement of proliferation of lineage-committed MPCs and for mobilization of MPCs to the blood. CCR1 is not a dominant receptor for MIP-1 suppression of MPC proliferation, but it does negatively impact G-CSF–induced MPC mobilization.

Key Words: CC chemokine receptor 1 • macrophage inflammatory protein 1 • progenitor cells • proliferation • mobilization

CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

Home | Help | Feedback | Subscriptions | Archive | Search

TABLE OF CONTENTS